The object of the proposed studies is to provide needed information in man on the metabolic pathways involved in the conversion of cholesterol to bile acids and their regulation. Further elucidation of bile acid pathways will involve additional studies on the mechanism of oxidative conversion of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) to cholic. Specifically the 24 alpha- and 24 beta-hydroxy isomer of varanic acid will be tested for their ability to form to cholic acid in man. Previous experiments indicated that the 24 alpha-hydroxy isomer is a poor precursor suggesting that the reaction might be stereospecific. Other studies will be carried out in liver disease patients to obtain additional information on the nature of the defect at the initial stages of the bile acid pathway, i.e. feedback triggering mechanism or lack of lipoprotein free cholesterol substrate. The potential findings from the present studies may have important implications in elucidating certain key abnormalities of lipid metabolism in man.